Disruption of guinea pig urinary bladder permeability barrier in noninfectious cystitis.
Although most cell membranes permit rapid flux of water, small nonelectrolytes, and ammonia, the apical membranes of bladder epithelial umbrella cells, which form the bladder permeability barrier, exhibit strikingly low permeabilities to these substances. In cystitis, disruption of the bladder permeability barrier may irritate the bladder wall layers underlying the epithelium, causing or exacerbating inflammation, and increasing urinary frequency, urgency, and bladder pain. To determine the effects of inflammation on the integrity of the permeability barrier, guinea pigs were sensitized with ovalbumin, and the bladders were exposed subsequently to antigen by instillation on the urinary side. Inflammation of the bladder wall markedly reduced transepithelial resistance of dissected epithelium mounted in Ussing chambers and increased water and urea permeabilities modestly at 2 h and more strikingly at 24 h after induction of the inflammation. Transmission and scanning electron microscopy of bladders at 30 min and 24 h after antigen exposure revealed disruption of tight junctions, denuding of patches of epithelium, and occasional loss of apical membrane architecture. These permeability and structural effects did not occur in nonsensitized animals in which the bladders were exposed to antigen and in sensitized animals exposed to saline vehicle rather than antigen. These results demonstrate that inflammation of the underlying muscle and lamina propria can disrupt the bladder permeability barrier by damaging tight junctions and apical membranes and causing sloughing of epithelial cells. Leakage of urinary constituents through the damaged epithelium may then exacerbate the inflammation in the underlying muscle layers.
Lavelle
J P
JP
Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Apodaca
G
G
Meyers
S A
SA
Ruiz
W G
WG
Zeidel
M L
ML
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002645:Chickens; D003556:Cystitis / Q000503:physiopathology*; D004058:Diffusion; D004848:Epithelium / Q000502:physiology / Q000503:physiopathology / Q000648:ultrastructure; D006168:Guinea Pigs; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009761:Nystatin / Q000494:pharmacology; D010047:Ovalbumin; D010539:Permeability; D014508:Urea / Q000493:pharmacokinetics; D001743:Urinary Bladder / Q000502:physiology* / Q000503:physiopathology* / Q000648:ultrastructure
D009761:Nystatin; D014508:Urea; D010047:Ovalbumin